Sustained
responses to interferon-alpha occur in 10% to 25% of patients with chronic
hepatitis C, but the long-term outcome is not well defined. We evaluated the
long-term clinical, histological, and virological outcomes of10 patients with
chronic hepatitis C who were treated between 1984 and 1987 with
interferon-alpha-2b for 52 +/- 6 weeks (total doses of 492 +/- 116 MU).

Before
therapy, all 10 had hepatitis C virus (HCV) RNA, elevations of serum
aminotransferases, and chronic hepatitis with fibrosis on liver biopsy. Clinical
follow up was 6 to 13 years, and liver biopsies were done 5 to 11 years after
initiation of therapy. HCV RNA was assayed by qualitative and quantitative
reverse transcriptase-polymerase chain reaction assays.

Among
5 patients who had a 6-month sustained response after therapy, all remained HCV
RNA negative, and at last follow-up, 4 had normal and 1 minimally elevated serum
aminotransferase levels. Liver biopsy specimens were nonreactive for HCV RNA,
and all the patients showed improvements in both inflammation and fibrosis and
were either normal or had mild, nonspecific inflammatory changes.

Among
5 patients without a sustained response, all continued to have HCV RNA in serum
and persistent or intermittent aminotransferase elevations. Liver biopsy
specimens showed little or no change in necrosis and inflammation; all except 1
patient had progression of fibrosis scores or cirrhosis. All 5 patients had
symptoms of chronic hepatitis, 1 underwent liver transplantation, and another
had progressive hepatic decompensation. In conclusion, patients with a 6-month
posttreatment virological response have a favorable long-term clinical and
histological outcome.

BACKGROUND:
Less than 20% of patients with chronic hepatitis C have a sustained response to
interferon-alpha therapy. The long-term benefit ofinterferon-alpha
with regard to hepatic viral clearance and histologic improvement remains
unknown. OBJECTIVE: To determine the long-termbiochemical,
virologic, and histologic outcomes in patients with chronichepatitis C who have
a sustained response to interferon-alpha therapy.

DESIGN:
Prospective cohort study. SETTING: University hospital.

PATIENTS:
80 patients who had chronic hepatitis C, had a sustained biochemical and
virologic response to interferon-alpha therapy, and were followed for at least
12-months.

RESULTS:
The 80 patients had follow-up 1 to 7.6 years (mean +/- SD, 4.0 +/- 2.0 years)
after interferon-alpha treatment. The follow-up period was 1, 2, 3, 4, 5, 6, and
more than 6 years in 11, 13, 14, 18, 10, 12, and 2 patients, respectively, after
the end of therapy. During the entire follow-up period, 93% (95% CI, 84% to 97%)
of patients had persistently normal serum ALT levels.
Serum HCV RNA remained undetectable in 96% (CI, 89% to 99%) of patients. A
comparison of liver histologic findings before and 1 to 6.2 years after
interferon-alpha treatment showed a clear improvement in 94% (CI, 83% to 99%) of
patients. In 62% of patients, the last biopsy done showed normal or nearly
normal histologic findings. Liver HCV RNA was detectable before treatment in
all 13 patients tested and was undetectable 1 to 5 years after treatment in all
27 patients tested.

CONCLUSIONS:
In patients with chronic hepatitis C who have persistently normal serum ALT
levels and no detectable serum HCV RNA 6 months after interferon-alpha therapy,
a long-term sustained biochemical and virologic response is generally seen. This
response is associated with an absence of detectable intrahepatic HCV RNA and
marked histologic improvement.